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The surface modification of two-dimensional (2D) nanocontainers with versatile chemical functionalities offers enormous advantages in medicine owing to their altered physicochemical ...properties. In this study, we demonstrate the fabrication of surface-functionalized layered double hydroxides (LDHs) towards their use as effective intestinal bile acid sequestrants. To demonstrate these aspects, the LDHs are initially modified with an amino silane, N1-(3-trimethoxysilylpropyl) diethylenetriamine (LDHs-N3),which, on the one hand, subsequently used for the fabrication of the dendrimer by repetitive immobilization of ethylene diamine using methyl acrylate as a spacer. On the other hand, these surface-functionalized LDHs are wrapped with an anionic enteric co-polymer to not only prevent the degradation but also increase the stability of these 2D nanoplates in an acidic environment of the stomach to explore the in vivo efficacy. In vitro cholic acid adsorption results showed that these surface-functionalized LDHs displayed tremendous adsorption ability of bile salt. Consequently, the bile salt adsorption results in vivo in mice confirmed that the enteric polymer-coated diethylenetriamine silane-modified LDHs, resulting in the reduced cholesterol by 8.2% in the high fat diet-fed mice compared to that of the oil treatment group with augmented 28% of cholesterol, which gained weight by 6.7% in 4 weeks. Notably, the relative organ (liver and kidney) weight analysis and the tissue section of histology results indicated that the modified LDHs showed high biocompatibility in vivo. Together, our findings validate that these surface-functionalized 2D nanoplates have great potential as effective intestinal bile acid sequestrants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper introduces an automatic approach to understand the purposes of each sentence in the abstract of an academic document. Specifically, computers can label each sentence in the abstract as ...being related to one or several of six aspects - "BACKGROUND", "OBJECTIVES", "METHODS", "RESULTS", "CONCLUSIONS", and "OTHERS". Experimental results obtained on a real dataset show that the labeling methodology outperforms baseline methods. We also build a prototype academic search engine to demonstrate the use of this new design. Users may search for articles containing keywords related to any of these six aspects to better meet their search goals.
Highly transparent photovoltaics (TPVs) integrated to a battery with small capacity can efficiently drive low‐powered internet of things (IoT) devices such as the receivers, sensors, actuators, etc. ...Such see‐through solar technology not only provides an opportunity to convert ambient light (sunlight or indoor lighting) to electricity but also demonstrates a concept of self‐sustainable power. In this work, a selective ultraviolet/near‐infrared bulk‐heterojunction active layer, i.e., chloroaluminum phthalocyanine (ClAlPc) as donor and C60 as acceptor with a Cu:Ag/WO3 transparent electrode to visible lights are combined for achieving the vacuum‐deposited TPVs with a power conversion efficiency of 1.34%, average visible transmission of 77.45%, and color rendering index of 91.9. Moreover, a TPV module with a working area of 1.5 cm2 is able to charge a 0.58 mAh LiFePO4(LFP)//Li battery fully within one hour under 100 mW cm‐2 (≈1 sun) illumination. The TPV module can drive an exciplex organic light‐emitting diode with the electroluminescence >180 cd m−2 at low illumination intensity of <5 mW cm‐2. Overall, this work presents a significant step forward in the development of TPV technology towards integrating a display and storage battery, which could be successfully applied in wearable electronics requiring invisible and sustainable solar power.
Transparent photovoltaics (TPVs) following the structure of indium tin oxide /MoO3/ClAlPc:C60/BCP/Cu:Ag/WO3 are developed, which offer high average visible transmission of 77.45% with color rendering index of 91.9 and power conversion efficiency of 1.34%. Moreover, the TPV module can fully charge a 0.58 mAh LiFePO4(LFP)//Li battery, and directly drive an exciplex organic light‐emitting diode with a luminance of 180 cd m−2.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cisplatin-based chemotherapy is the first line treatment for several cancers including bladder cancer (BC). Autophagy induction has been implied to contribute to cisplatin resistance in ovarian ...cancer; and a high basal level of autophagy has been demonstrated in human bladder tumors. Therefore, it is reasonable to speculate that autophagy may account for the failure of cisplatin single treatment in BC. This study investigated whether cisplatin induces autophagy and the mechanism involved using human BC cell lines.
Human BC cells (5637 and T24) were used in this study. Cell viability was detected using water soluble tetrazolium-8 reagents. Autophagy induction was detected by monitoring the levels of light chain 3 (LC3)-II and p62 by Western blot, LC3-positive puncta formation by immunofluorescence, and direct observation of the autophagolysosome (AL) formation by transmission electron microscopy. Inhibitors including bafilomycin A1 (Baf A1), chloroquine (CQ), and shRNA-based lentivirus against autophagy-related genes (ATG7 and ATG12) were utilized. Apoptosis level was detected by caspase 3/7 activity and DNA fragmentation.
Cisplatin decreased cell viability and induced apoptosis of 5637 and T24 cells in a dose-and time-dependent manner. The increased LC3-II accumulation, p62 clearance, the number of LC3-positive puncta, and ALs in cisplatin-treated cells suggested that cisplatin indeed induces autophagy. Inhibition of cisplatin-induced autophagy using Baf A1, CQ, or ATG7/ATG12 shRNAs significantly enhanced cytotoxicity of cisplatin toward BC cells. These results indicated that cisplatin induced protective autophagy which may contribute to the development of cisplatin resistance and resulted in treatment failure. Mechanistically, upregulation of beclin-1 (BECN1) was detected in cisplatin-treated cells, and knockdown of BECN1 using shRNA attenuated cisplatin-induced autophagy and subsequently enhanced cisplatin-induced apoptosis.
Collectively, the study results indicated that cisplatin-induced autophagy is mediated by BECN1 in BC cells. Therefore, combinative treatment using cisplatin and autophagy inhibitors could potentially overcome cisplatin resistance related to autophagy induction.
Sepsis develops as a result of the host response to infection, and its mortality rate in ICU remains high. Severe inflammation usually causes overproductions of proinflammatory cytokines, i.e., TNF-α ...and reactive oxygen species, which lead to mitochondrial damage and energetic depletion. Autophagy is a survival mechanism for eukaryote to recycle intracellular nutrients and maintain energy homeostasis. We hypothesize that autophagy plays a beneficial role in the pathogenesis of organ failure during sepsis. A rat model of cecal ligation and puncture (CLP) that simulate peritonitis-induced sepsis was used, and indicators for liver dysfunction, serum glutamic oxaloacetic, serum glutamic pyruvic, alkaline phosphatase, and bilirubin were measured. Levels of LC3-II and LC3 aggregation were quantified by Western blot analysis and by immunohistochemistry, respectively. The tissue localization of autophagy was identified by immunohistochemistry and transmission electron microscopy. Our results showed that (a) increase in LC3-II level in liver tissue occurs at 3 h, peaks at 6 h, and then surprisingly declines quickly until 18 h after CLP (CLP18h); (b) significant hepatic dysfunction was observed at CLP18h; (c) ratio of LC3 aggregation is significantly higher in hepatocytes than in Kupffer cells, and (d) loss of Atg7, an essential gene for autophagosome formation, exaggerates the TNF-α-induced cell death, depletion of ATP, and decrease of albumin production in hepatocytes. These results indicate that autophagy occurs transiently in hepatocytes at early stage, and the decline in autophagy at late stage may contribute to the functional failure in liver during polymicrobial sepsis.
In this work, we demonstrate the high-power and high-responsivity performance of the dual multiplication (M-) layers in In0.52 Al0.48 As based avalanche photodiode (APD). The dual M-layer design in ...our APD structure effectively constrains the multiplication process to a thin high-field region rather than the whole thick M-layer. It thus minimizes the space charge effect (SCE) within and avoids increasing the tunneling dark current for the case of directly shrinking M-layer thickness in APD. Furthermore, by combining the specially designed mesa shape with this dual M-layer structure, the edge breakdown can be well suppressed. These benefits lead to an ultra-high gain-bandwidth product (450 GHz; 1 A/W at unit gain) and a high saturation current (>12 mA) can be simultaneously achieved in our device. By nonlinearly driving a wavelength sweeping laser in the self-heterodyne lidar setup, it can generate an optical pulse train-like waveform, providing an effective optical modulation depth of 200% to feed into our demonstrated APD at the receiver-end. Under such scheme, the photo-generated RF (1 GHz) power from our APD with a 6.3 A/W responsivity can be as high as +6.95 dBm at a high (7 mA) output photocurrent. Such high-power and high-responsivity characteristics of our APD can further improve the signal-to-noise (S/N) ratio and dynamic range performances in each pixel of the lidar image. A high-quality 3-dimensional (D) FMCW lidar image is constructed based on our APD, without the integration of any electrical amplifier at the receiver end.
Carnosic acid (CA), a natural catechol rosin diterpene, is used as an additive in animal feeds and human foods. However, the effects of CA on mammalian reproductive processes, especially early ...embryonic development, are unclear. In this study, we added CA to parthenogenetically activated porcine embryos in an in vitro culture medium to explore the influence of CA on apoptosis, proliferation, blastocyst formation, reactive oxygen species (ROS) levels, glutathione (GSH) levels, mitochondrial membrane potential, and embryonic development-related gene expression. The results showed that supplementation with 10 μM CA during in vitro culture significantly improved the cleavage rates, blastocyst formation rates, hatching rates, and total numbers of cells of parthenogenetically activated porcine embryos compared with no supplementation. More importantly, supplementation with CA also improved GSH levels and mitochondrial membrane potential, reduced natural ROS levels in blastomeres, upregulated Nanog, Sox2, Gata4, Cox2, Itga5, and Rictor expression, and downregulated Birc5 and Caspase3 expression. These results suggest that CA can improve early porcine embryonic development by regulating oxidative stress. This study elucidates the effects of CA on early embryonic development and their potential mechanisms, and provides new applications for improving the quality of in vitro-developed embryos.
Summary Background Prostate cancer (PCa) is a leading cause of cancer-related death in men, which emphasizes the need for novel therapeutic approaches. Targeting microRNA (miRNA) has been considered ...as a therapeutic strategy against cancers. Human miR-204-5p potentially targeting BCL2 has been reported to be downregulated in various cancers. We hypothesized that miR-204-5p overexpression induces cancer cell apoptosis by repressing BCL2 expression. Methods A vector harboring mature miR-204-5p was constructed and delivered into human PCa cells. The expression level of miR-204-5p was determined by miRNA quantitative polymerase chain reaction (QPCR). Luciferase reporter assays were performed to verify the function of mature miR-204-5p and its direct binding to BCL2 transcripts. The expression levels of BCL-2 messenger RNA (mRNA) and protein samples were measured by QPCR and Western blot, respectively. Cell viability was detected by WST-1 assays. Induction of apoptosis was determined by increased levels of cleavage caspase 3 and caspase 3/7 activity. Results The expression levels of miR-204-5p were downregulated in PCa cells compared with normal prostate epithelial cells. Transfection of pSM-204 resulted in up to 6.2-fold higher expression of miR-204-5p when compared with pSM control. The mRNA levels of several potential target genes of miR-204-5p were decreased in pSM-204-transfected PC3 and Rv1 cells. BCL2 mRNA and protein expression decreased in miR-204-5p-transfected cells, which led to cytochrome C release from mitochondria. It subsequently increased cleaved caspase 3 and caspase 3/7 activities and reduced cell viability. Cotransfection of a reporter vector harboring the BCL2 3′-untranslated region to compete with endogenous transcripts partially rescued miR-204-5p-induced apoptosis. Conclusion Human miR-204-5p targets BCL2 in PCa cells. Restoration of miR-204-5p in PCa could therefore be considered as a novel strategy by targeting antiapoptotic BCL2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study examined the effectiveness of various vaccine policies against influenza. The transmission rate was calculated by use of the time-series influenza-like illness case during the year of 2009 ...and recent epidemics in Taiwan.
We developed a stochastic compartmental model to analyze the transmission of influenza, where the population was stratified by location and age group, and the vaccine distribution was considered using the current policy. The simulation study compared the previous vaccine policy and a new policy with expanded coverage and various lengths of the vaccination campaign. The sensitivity analysis investigated different levels of vaccine efficacy to confirm the robustness of the recommended policies.
Doubling vaccine coverage can decrease the number of infections effectively in the regular epidemic scenario. However, a peak of infections occurs if the duration of implementing vaccination is too long. In the 2009-like pandemic scenario, both increasing vaccine doses and reducing the program's duration can mitigate infections, although the early outbreak restricts the effectiveness of vaccination programs.
The finding indicates that only increasing vaccine coverage can reduce influenza infections. To avoid the peak of infections, it is also necessary to execute the vaccination activity immediately. Vaccine efficacy significantly impacts the vaccination policy's performance. When vaccine efficacy is low, neither increasing vaccination doses nor reducing vaccination timeframe prevents infections. Therefore, the variation in vaccine efficacy should be taken into account when making immunization policies against influenza.
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